Effect of Memantine Hydrochloride on Homocysteine Level and Cognitive Function in Diabetic Vascular Dementia Model Mice

2021 ◽  
Vol 11 (5) ◽  
pp. 872-878
Author(s):  
Yu Yang ◽  
Lifei Xing ◽  
Hongliang Yan ◽  
Min Wang ◽  
Yanqing Huang ◽  
...  

Increased Hcy has a toxic effect on nerve cells and can cause hippocampal death and directly damage the body’s cognitive function and memory ability, leading to the occurrence of vascular dementia. Hcy predicts vascular disease and might be a basis for clinical judgment. This article provides a new basis for the prevention and treatment of this disease by exploring the mechanism of action of memantine hydrochloride in diabetic vascular dementia. After grouping, mice walked through the Morris water maze to record the escape latency, and measured the Hcy level of the mice by high performance liquid chromatography. Observing the volume of brain atrophy in mice. GFAPT, APP, and CHAT level in mouse hippocampus was assessed by IHC and CHAT mRNA was detected by RT-PCR. Escape latency, Hcy level (11.46 ±0.74) yiimmol/L, brain atrophy volume (25.21 ±1.21) mm3, number of APP positive cells (46.7003±3.2431), number of GFAP positive cells (21.4000 ± 1.8127) were all significantly lower than those of model group. The positive rate of CHAT and the amount of CHAT mRNA in the memantine hydrochloride group was significantly elevated (P < 0.05) with higher CHAT mRNA than model group and lower than blank group (P < 0.05). Memantine hydrochloride could reduce the level of Hcy in mice, improve the cognitive function of mice with diabetic vascular dementia by improving the number of GFAP and CHAT positive cells in hippocampus and cortex, and increasing the amount of CHAT mRNA in brain tissue.

2020 ◽  
Vol 19 (4) ◽  
pp. 823-828
Author(s):  
Ang Cai ◽  
Liu Xiao ◽  
Yan-Ping Zhou ◽  
Zhi-Guo Zhang ◽  
Quan-Wei Yang

Purpose: To investigate the protective effect of Evodia rutaecarpa (Juss.) Benth. extract (ERBE) against Alzheimer's disease in 3xTg-AD mice. Methods: The cognitive function of 3xTg-AD mice was assessed using Morris water maze test. The levels of amyloid beta deposits and NeuN in the mouse hippocampus were evaluated by immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were determined by western blot analysis. Results: ERBE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. The escape latency in the animals treated with 400 mg/kg ERBE (20.5 ± 1.3 s) was significantly higher than untreated 3xTg-AD mice (12.4 ± 1.3 s, p < 0.01). In addition, ERBE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expressions of BDNF (1.4 ± 0.2, p < 0.05) and TrkB (1.1 ± 0.2, p < 0.05) in 3xTg AD mice. Conclusion: The results suggest that ERBE administration may be a useful strategy for treating memory impairment induced by several neurodegenerative diseases. Keywords: Evodia rutaecarpa, Alzheimer, Memory impairment, NeuN-positive cells


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Lue Ha ◽  
Bin Yang ◽  
Shaosong Wang ◽  
Yu An ◽  
Hao Wang ◽  
...  

Objective. To observe the effect of moxibustion on cognitive function of aging mice, to observe the effect of moxibustion on protein and gene expression of APP metabolism pathway, and to explore the mechanism of action in moxibustion. Methods. 24 SAMP8 were randomly divided into 2 groups (12 in each group): moxibustion group and model group. 12 SAMR1 mice were used as blank controls. Mice in the moxibustion group were treated with moxibustion for 8 weeks, 10 minutes each time, 5 times a week, and for a total of 8 weeks. The model group and the blank group were treated with sham-moxibustion. Behavior tests were used to detect the learning and memory ability of each group of mice. Immunohistochemical, western blot, and RT-PCR were used to detect the protein and mRNA expression of APP and BACE1. Furthermore, the expressions of miR-29 and miR-101 were observed by RT-PCR method to explore the mechanism of moxibustion at the genetic level. Results. In this study, relative to normal mice, we found that aging mice showed behavioral changes consistent with the onset of AD. However, moxibustion interventions were able to mitigate these effects to some degree in aging mice. In addition, moxibustion was proved to regulate APP metabolism pathway at protein and gene level through molecular biology tests. Conclusion. The data suggest that the effect of moxibustion intervention on cognitive function in aging mice is related to the regulation of genes and proteins involved in APP metabolism pathway; this may be a potential target for treating Alzheimer’s disease.


Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 202
Author(s):  
Yexin Dai ◽  
Jie Ding ◽  
Jingyu Li ◽  
Yang Li ◽  
Yanping Zong ◽  
...  

In this work, reduced graphene oxide (rGO) nanocomposites doped with nitrogen (N), sulfur (S) and transitional metal (Ni, Co, Fe) were synthesized by using a simple one-step in-situ hydrothermal approach. Electrochemical characterization showed that rGO-NS-Ni was the most prominent catalyst for glucose oxidation. The current density of the direct glucose alkaline fuel cell (DGAFC) with rGO-NS-Ni as the anode catalyst reached 148.0 mA/cm2, which was 40.82% higher than the blank group. The DGAFC exhibited a maximum power density of 48 W/m2, which was more than 2.08 folds than that of blank group. The catalyst was further characterized by SEM, XPS and Raman. It was speculated that the boosted performance was due to the synergistic effect of N, S-doped rGO and the metallic redox couples, (Ni2+/Ni3+, Co2+/Co3+ and Fe2+/Fe3+), which created more active sites and accelerated electron transfer. This research can provide insights for the development of environmental benign catalysts and promote the application of the DGAFCs.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kouji Wakayama ◽  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Ryuichi Morishita

Background & Purposes: There had been no attempt to show the efficacy of therapeutic vaccination in vascular dementia. A rat model of vascular dementia was prepared by bilateral common carotid artery ligation (2VO). The purpose of this study is to investigate whether pre-exposure Angiotensin II (Ang II) peptide vaccination exhibits the protective effects against white matter lesions (WML) in 2VO rats. Methods: After subcutaneous injection of Ang II peptide vaccine (10μg/200μl) or saline (200μl) to Wistar rats (male) at the time point of 6, 8 and 10 week-old, 2VO or sham surgery was performed at 12 week-old. Cognitive function was evaluated after 14 days of 2VO using the novel object recognition (NOR) test. Anti-Ang II antibody (Ab) level was quantified using ELISA. Histological examinations of WML and demyelination in the corpus callosum (CC) were evaluated using immunohistochemistry (IHC), 5-bromodeoxyuridine (BrdU) assay and Klüver-Barrera staining. Western blot analyses of VCAM-1, FGF2, phospho-CREB and CREB using proteins extracted from CC were performed to investigate the mechanism of restoration of WML by Ang II vaccination. Results: Histological examinations presented that exacerbation of WML and demyelination observed in saline treated (S) rats was ameliorated in Ang II vaccinated (V) rats. The results of NOR test indicated that cognitive dysfunction observed in S rats was improved in V rats at 14 days after 2VO. Expression of VCAM-1 in CC of S rats was significantly reduced in V rats at 7 days after 2VO. BrdU assay exhibited that vaccination accelerated the differentiation of oligodendrocyte progenitor cells (OPCs) in WML from 14 days to 28 days of 2VO. Western blot presented that both CREB phosphorylation and FGF2 expression in CC were increased in V rats compared with S rats at 14 days after 2VO. Double IHC showed that FGF2 expressing cells were mostly endothelial cells and astrocytes in WML. Conclusions: Ang II vaccination restored WML as well as cognitive function in 2VO rats. Our findings suggested that Ang II vaccination ameliorated cerebrovascular endothelial dysfunction which could accelerate the OPCs differentiation through increased expression of FGF2 in endothelial cells or astrocytes in 2VO rats.


2015 ◽  
Vol 23 (3) ◽  
pp. S74-S75
Author(s):  
Aiying A. Xiao ◽  
Martin Durkin ◽  
Imran Iftikhar ◽  
Shilpa Srinivasan

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S217-S218
Author(s):  
Jimmy Lee ◽  
Jie Yin Yee ◽  
Yuen Mei See ◽  
Charmaine Tang ◽  
Boon Tat Ng ◽  
...  

Abstract Background Clozapine remains the only antipsychotic with unique efficacy in treatment resistant schizophrenia (TRS). Considerable ongoing research and clinical efforts have focused on reducing barriers to clozapine use in a bid to increase rates of clozapine use to improve outcomes in TRS. However, less than half of individuals with TRS respond to clozapine, with the remainder categorised as clozapine resistant (CRS) or Ultra-resistant. It is important to deepen understanding on the development of CRS so we can identify them early, attempt to prevent/delay its onset and also explore novel treatments. In the present study, we sought to compare clozapine responders from CRS and identify factors which might be associated with CRS. Methods This study was conducted at the Institute of Mental Health, the only psychiatric facility with clozapine services in Singapore. Individuals with TRS on clozapine for at least 12 weeks and the capacity to give informed consent were enrolled into the study. Each participant underwent a clinical assessment on the Structured Clinical Interview DSM-IV-TR (SCID), Positive and Negative Syndrome Scale (PANSS) and Social Occupational Functioning Assessment Scale (SOFAS). We applied the Treatment Response and Resistance In Psychosis consensus criteria to define clozapine response and resistance. Brief Neurocognitive Assessment was done using the digit sequencing and symbol coding tasks from the Brief Assessment of Cognition in Schizophrenia (BACS). A fasting sample of blood was collected; assays for clozapine and norclozapine were performed using high performance liquid chromatography. To be classified as CRS, a participant must meet the below criteria: (i) not meeting symptom remission criteria on the PANSS using the Remission in Schizophrenia Working Group criteria, (ii) moderate and lower level of functioning on the SOFAS, and (iii) at least 12 weeks of clozapine treatment and plasma clozapine levels ≥ 350 ng/ml. Results A total of 91 participants were enrolled in this study and 67 (73.6%) met criteria for CRS. 1 in 4 clozapine responders had plasma clozapine levels not exceeding 350 ng/ml. There were no significant differences in age, sex, smoking status, age at onset of illness, clozapine adherence, antipsychotic polypharmacy rates and duration of clozapine use between clozapine responders and CRS. Compared to clozapine responders, individuals with CRS had statistically significantly lower BMI (26.4 vs. 23.4, p=0.008) lower rates of employment (79.2% vs. 35.8%, p&lt;0.001), and poorer cognitive function in both digit sequencing (-0.86 vs. -1.60, p=0.011) and symbol coding (-1.09 vs. -1.88, p=0.002) tasks. In a multivariate logistic regression model with age, sex, age at onset, BMI and cognition, only BMI (OR=0.88, p=0.043) and symbol coding (OR=0.48, p=0.019) were significant variables predicting clozapine resistance. Discussion Our study highlighted a high rate of CRS and suggests that poorer cognitive function, specifically in processing speed, might be associated with the development of clozapine resistance in schizophrenia. Additionally, it was interesting to note that a higher BMI was associated with clozapine response; this lends weight to existing metabolic and lipid hypotheses of schizophrenia.


2020 ◽  
Vol 11 ◽  
pp. 204062232095335
Author(s):  
Ke Zheng ◽  
Yujun Qian ◽  
Tiaye Lin ◽  
Fei Han ◽  
Hui You ◽  
...  

Background: Carotid intima–media thickness (cIMT) is considered a risk factor for and predictor of cerebrovascular disease. In this study, we explored the contribution of cIMT to cognitive impairment (CI) in dialysis patients and the role of cerebral small vascular disease (CSVD) and brain atrophy in this process. Methods: Cognitive function was assessed using a comprehensive cognitive test battery. CSVD and brain volume were assessed by magnetic resonance imaging, and cIMT was measured by ultrasonography. Multivariable analysis and mediation were used to explore the relevant relationships among cIMT, CI, CSVD and brain volume. Results: Seventy-three dialysis patients were enrolled. Approximately 54.8% were diagnosed with increased cIMT. The increased cIMT group was older and had lower serum albumin and creatinine levels than the normal cIMT group. There was no difference in the CSVD prevalence between the different cIMT groups. Patients in the normal, unilaterally and bilaterally increased cIMT subgroups demonstrated a gradual decrease in brain-matter volume and degenerate cognitive function. cIMT was related to cognitive function and gray-/white-matter volume. Increased cIMT was associated with a significantly increased risk of a reduced Mini Mental State Examination/Montreal Cognitive Assessment score and Trail A/B time delay. Mediation analysis showed that CI was mediated by brain-matter volume but not by CSVD. Conclusion: Increased cIMT was an independent risk factor for impairment of global cognitive function, memory, and executive function. The impact of cIMT on cognition was not induced by CSVD but by brain atrophy. cIMT may be a useful tool for screening patients at high risk of CI in the dialysis population.


2016 ◽  
Vol 12 ◽  
pp. P418-P419
Author(s):  
Hairong Qian ◽  
Linling Mao ◽  
Chongfeng Bi ◽  
Lijun Peng ◽  
Deyu Xia

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